Muscular fatigue during exercise is the inability to continue to perform at the same level of intensity, resulting from the inability of the muscles to produce force. Fatigue may occur during both aerobic and anaerobic exercise, and at submaximal effort depending on the ambient temperature, hydration status, electrolyte concentrations, external motivation, and the animal's desire to work. As effort increases, glycogen depletion, intracellular acidosis, and accumulation of metabolic by-products will contribute to the onset of fatigue. Fatigue during exercise can also be the result of pathologic conditions, including diseases that affect oxygen uptake, energy metabolism, or neuromuscular function. This chapter will focus on muscular fatigue in normal, healthy animals.
Fatigue is considered a normal consequence of exercise of prolonged duration or high intensity, and is regarded as an intrinsic safety mechanism. Without the onset of fatigue, or if fatigue is delayed for a time, structural damage to the myocytes and supportive tissues may occur. Most knowledge of fatigue has been described in horses using high-speed treadmill exercise, to allow for investigation of the respiratory, cardiovascular, and metabolic responses during exertion. Tests involved include spirometry, arterial blood gases, hematologic analysis, kinematics, electromyography, and muscle biopsies. Fatigue in these studies has been defined as the inability or unwillingness of the horse to maintain the same velocity as the treadmill at a determined speed despite minimal encouragement. Horses run to the point of fatigue on a treadmill exhibit characteristic changes in gait, including decreased stride frequency and a longer stride length.
Fatigue has been classified into two types: peripheral and central. Peripheral fatigue is described as fatigue secondary to altered muscle function. The primary cause is failure of ATP to resynthesize with accumulation of ADP and inorganic phosphate ions. Studies of muscle metabolism after exercise to identify peripheral fatigue have relied mainly on muscle biopsies and direct measurement of muscle glycogen, creatine phosphate, ATP, ADP, inosine monophosphate, inorganic phosphate, glycolytic intermediary products, pH, and other metabolites. Other studies have investigated the expression of mRNA in muscle tissue to monitor adaptations in gene expression of proteins that regulate oxygen-dependent metabolism, glucose metabolism, and fatty acid utilization. Indirect serum biomarkers associated with fatigue may include lactate, ammonia, hypoxanthine and xanthine, ammonia, markers of oxidative damage (thiobarbituric acid reactive substances, glutathione, and glutathione peroxidase), inflammatory mediators, and lymphocytes.
Central fatigue is defined as an alteration in the signals arising from the CNS, directly decreasing performance by modifying the frequency of the action potential in the motor neurons. Central fatigue may occur secondary to pain, dyspnea, perceptions of exertion, hypoglycemia, hyperthermia, ammonia accumulation, increases in serotonin, altered amino acid metabolism, and changes in extracellular ions. Central fatigue is associated with decreased motivation, lethargy, tiredness, and loss of muscle coordination. However, the cause of central fatigue is multifactorial, and the response to these stimuli is highly variable. For example, some horses can continue endurance exercise at speed despite severe hyperthermia, dehydration, and plasma electrolyte disturbances.
Last full review/revision January 2014 by Amelia S. Munsterman, DVM, MS, DACVS, DACVECC